Christian Cadeddu Dessalvi

Gender determinants of cardiovascular risk factors and diseases.

This article addresses the various aspects concerning gender dissimilarities in the cardiovascular system. It examines sex differences in the genetic susceptibility to cardiovascular disease (CVD) development or outcome: with the presence of either XX or XY chromosomes, every cell is sexually differentiated and there exist postpuberal differences between male and female cardiovascular systems. The main action mechanisms of sex steroid hormones are discussed, mainly as to testosterone (Te) in men and 17beta-estradiol (E2) and progesterone (Pro) in women. In women, susceptibility to CVD is known to increase in the postmenopausal period, when the ovarian hormone function expires. Some concepts of the sex-based differences in anatomy and physiology are also explained. Although they have the same structural elements, women and men use them in a different way to guarantee cardiovascular system homeostasis. Some examples of differences between men and women in pathological cardiovascular function are given. A further important issue regards the prevalence and role of cardiovascular risk factors in the two genders. Compared to boys of the same age, adolescent girls and premenopausal women have a more favorable risk profile: lower blood pressure (BP), less atherogenic lipid profile, and lower prevalence of cardiovascular risk factors. Women develop CVD later than men and diabetic women have a considerably higher mortality rate compared to men of the same age. Finally, there exist several clinically significant differences between men and women as to prevalence, presentation, management and outcome of CVD. Clinical peculiarities related to gender in presentation of some CVDs, such as coronary heart disease (CHD), stroke and heart failure, are described. We are absolutely convinced that only an accurate knowledge of the sex-specific pathophysiology may allow determination of the appropriate diagnostic instruments and to implement tailored treatments of CVD in men and women.

Potential cardiac risk of immune-checkpoint blockade as anticancer treatment: What we know, what we do not know, and what we can do to prevent adverse effects

Cancer immunotherapy has become a well‐established treatment option for some cancers after the development of a family of drugs targeting the so‐called immune checkpoints, such as CTLA4 and PD‐1 with PD‐L1. These co‐receptors/ligands inhibit the activation of T‐cell, thus preventing an excessive inflammatory response. Tumors exploit these pathways to induce immune tolerance to themselves. Thus, the main effect of checkpoint‐blocking drugs is to awake an immune response primarily directed against cancer cells. Nonetheless, as the immune response elicited by these drugs is not completely tumor‐specific, their use may actually cause several adverse effects, including adverse cardiovascular effects. In this review, we will discuss the principles and potentiality of immunotherapy for cancer treatment, the experimental and clinical data on the role of CTLA4 and PD‐1 with PD‐L1 as immune‐checkpoints in the cancer environment and in the cardiovascular system, and strategies aimed at preventing possible cardiovascular adverse effects of immune‐checkpoint blockers.

Diastolic Function in Systemic Sclerosis Patients

S ystemic sclerosis (SSc) is a highly heterogeneous disease related to the production of autoantibodies and increased deposition of extracellular matrix. Although SSc affects the whole organism, its prognosis is mainly linked to cardiovascular damage (1). The pathophysiological cascade in SSc seems to involve impaired interplay between fibroblasts and both endothelial and epithelial cells, followed by lymphocyte activation, autoantibody production, inflammation, and finally fibrosis, with accumulation of extracellular matrix and replacement of normal tissue culminating in organ failure (2). There has been much discussion about what factor most influences the prognosis in patients with SSc. Initially, the focus was on renal crisis and then, after the introduction of angiotensin-converting enzyme inhibitors, interstitial lung disease and pulmonary arterial hypertension (PAH) (3). In recent years, the focus has shifted from systolic dysfunction of the left ventricle to alteration of the pulmonary circulation with secondary pulmonary hypertension and impairment of the right ventricle. For years, PAH was the first concern of rheumatologists, with the involvement of the pulmonary microcirculation widely recognized as the most important negative prognostic factor. The exact mechanisms underlying development and progression of SSc-PAH remain unclear, but inflammation and endothelial injury can trigger a pathophysiological

Metabolomic Approach to Redox and Nitrosative Reactions in Cardiovascular Diseases

Metabolomics, also referred to as metabonomics, is one of the most recent innovative technologies in medicine. It offers a direct functional read-out of phenotypes by the detection, identification, and quantification of a large number of metabolites within a biological sample such as urine and blood. Metabolites (<1500 Da) represent the output of cellular metabolism, accounting for expression and activity of genes, transcripts, and proteins, and offering unique insights into small molecule regulation, which may uncover new biochemical patterns. Metabolomics research has considerable potential for translating the metabolic fingerprint into personalized therapeutic strategies. Within the field of interest, cardiovascular disease (CVD) is one of the most developed areas. However, CVD remains the leading cause of death worldwide with a marked increase in mortality rates over the past six decades. In this scenario, recent findings indicate the important role of redox and nitrosative (RN) reactions in CVD development and progression. RN reactions are generally involved in the homeostatic modulation of a wide number of cellular and organ functions. Conversely, the imbalance of these reactions may lead to a condition of allostasis that in turn can cause CVD. The aim of this review is to highlight how the use of metabolomics may be useful for the study of RN reactions related to CVD, providing a tool to understand the mechanisms underlying reactions that could lead to impaired ROS or RNS formation.